Clopidogrel (methyl(S)-(+)-α-(2-chlorophenyl)-6,7-dihydrothieno[3,2-a]pyridine-5(4H)-acetate) of formula (IV), which has inhibiting activity against platelet agglutination, is a useful vascular diseases therapeutic for treating peripheral artery diseases such as stroke, thrombosis and embolism, as well as ischemic heart diseases such as myocardial infarction and angina pectoris:

Clopidogrel, an optically active dextrorotatory compound, however, is an oil phase which is unstable under moist and high temperature conditions and is difficult to be purified to the level of required for pharmaceutical use.
Accordingly, acid addition salts of clopidogrel, which are stable solid and easy to purify, have been developed. Clopidogrel 1,5-naphthalenedisulfonate (napadisilate (INN)), one of the most stable acid addition salts, has been disclosed in International Publication No. WO 2005/097804, wherein clopidogrel 1,5-naphthalenedisulfonate is prepared by reacting the free base form of clopidogrel with 1,5-naphthalenedisulfonic acid.
However, 1,5-naphthalenedisulfonic acid used in the above method (Armstrong acid) is a strong acid having a pKa1 value of −3.37 and a pKa2 of −2.64, and is not suitable for use in the preparation of high quality clopidogrel 1,5-naphthalenedisulfonate due to its corrosiveness, handling in a bulk production process and tendency to color the product red. Accordingly, there has been a need for an improved method of preparing clopidogrel 1,5-naphthalenedisulfonate.
The present inventors have found that clopidogrel 1,5-naphthalenedisulfonate can be beneficially prepared by reacting a clopidogrel acid addition salt with a 1,5-naphthalenedisulfonate, which is not acidic nor corrosive.